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|LETTER TO EDITOR
|Year : 2017 | Volume
| Issue : 2 | Page : 418-420
Craniopharyngioma with malignant transformation: Review of literature
S Narla1, J Govindraj2, K Chandrasekar3, P Sushama1
1 Department of Histopathology, Apollo Cancer Institutes, Chennai, Tamil Nadu, India
2 Department of Radiology, Apollo Cancer Institutes, Chennai, Tamil Nadu, India
3 Department of Neurosurgery, Apollo Cancer Institutes, Chennai, Tamil Nadu, India
|Date of Web Publication||10-Mar-2017|
Department of Histopathology, Apollo Cancer Institutes, Chennai - 600 035, Tamil Nadu
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Narla S, Govindraj J, Chandrasekar K, Sushama P. Craniopharyngioma with malignant transformation: Review of literature. Neurol India 2017;65:418-20
Craniopharyngioma is a relatively rare non-malignant non-glial intracranial tumor. From a histopathological perspective, these tumors are categorized into two variants – the adamantinomatous and the papillary varieties. The adamantinomatous type is the most common subtype affecting individuals in the first two decades of life, while the papillary craniopharyngioma is reported predominantly in adults. While the former represents the squamous cell rests of the embryonic craniopharyngeal duct, the latter subtype is the result of metaplastic adenohypophyseal cells. Craniopharyngioma represents 1.2–4% of all childhood intracranial tumors. Malignant transformation in a craniopharyngioma is extremely rare. Malignant craniopharyngioma may be of primary (that is developed de novo) or of secondary type (due to malignant transformation of a craniopharyngioma). It has been suggested that radiation therapy could be the inducing factor.
We report the case of a 28-year-old female patient who was admitted due to progressive bilateral visual disturbance and anosmia. There were no neurological deficits on examination. The patient had undergone two attempts at transcranial excision of a suprasellar craniopharyngioma at 7 and 14 years of age, respectively, and a single fraction of gamma knife radiation at 14 years of age (at another center). She was on hormonal supplementation therapy since the time of the previous treatment as a result of pituitary hypofunction. Magnetic resonance imaging (MRI) of the brain [Figure 1] showed a peripherally enhancing solid lesion in the suprasellar and parasellar regions, encasing the optic nerves as well as the optic chiasma. There was obstructive hydrocephalus due to compression of the third ventricle. The patient was taken up for surgery and a near-total excision of the tumor was achieved, considering that the tumor was close to the optic nerves. Microscopic examination of the surgical specimen showed a highly cellular neoplasm composed of multilayered, markedly atypical squamous cells with disruption of the basement membrane [Figure 2]. The cells showed an abundant eosinophilic cytoplasm, pleomorphic nuclei, and prominent nucleoli. Abundant mitotic figures and foci of necrosis were also present. The tumor showed areas of keratinization with abundant keratin admixed tumor lobules, some of which had an appearance of “wet keratin.” Immunohistochemical staining [Figure 2] showed a strong nuclear positivity for beta-catenin and p63 with strong membranous positivity for cytokeratin (CK) 5/6. Ki67 index was found to be 30–40%. The nuclear staining for beta-catenin in the context of clinical history supported a diagnosis of squamous cell carcinoma arising in an adamantinomatous craniopharyngioma. Postoperative positron emission tomography-computed tomography (PET-CT) scan showed an increased isotope uptake in the hypermetabolic areas of the residual tumor in the left parasellar region, without any evidence of metastasis elsewhere in the body. Stereotactic radiotherapy using cyberknife was delivered to the residual tumor in a dose of 45Gy. Later, the patient was lost to follow up.
|Figure 1: Postcontrast axial (a) and sagittal sections (b) of the cranial MRI showing a peripherally enhancing solid lesion in the suprasellar and parasellar regions, involving the optic nerves and chiasma with obstructive hydrocephalus|
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|Figure 2: Nests of atypical squamous cells (a, hematoxylin and eosin ×100). Abundant wet keratin closely admixed with the tumor cells (b, hematoxylin and eosin ×100). Tumor cells staining positive for p63 (c, immunohistochemistry ×100), Ki 67 proliferation index 30–40% (d, immunohistochemistry ×100)|
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Craniopharyngioma is a benign neoplasm affecting the sellar/suprasellar area. The patients usually present with visual and endocrine dysfunction. Their incidence has a bimodal distribution with peaks observed at 5–14 years, and again between 40–60 years of age. In childhood and adolescence, the adamantinomatous type with cyst formation is common whereas the squamous–papillary histologic type is more prevalent in adults. The pathogenesis of craniopharyngioma is poorly understood. To date, mutations in the beta-catenin gene have been reported in 77% of the craniopharyngiomas, exclusively of the adamantinomatous subtype. Beta-catenin is a key mediator of the WNT (Wingless integrated) signalling pathway, which is involved in the control of cell proliferation, differentiation, and migration. Despite being a WHO Grade I tumor, these tumors are difficult to completely resect, necessitating repeat surgeries or adjuvant radiation in many of them. Malignant transformation in a craniopharyngioma is an extremely uncommon phenomenon. The mechanisms for development of these so called “malignant or anaplastic craniopharyngiomas” is currently unknown. Nelson et al., showed a causal relationship between radiation therapy and malignant transformation in craniopharyngiomas. Animal research and in-vitro analysis of human tumors in general have demonstrated that the development of delayed p53 mutations following radiation may be one step in the process of development of radiation-induced neoplasms.
In the review of the literature, the patients with malignant craniopharyngiomas have ranged from 10 to 63 years of age (average: 28.4 years) without any specific gender predilection. The time interval from the detection of the primary tumor to the malignant transformation has ranged from 1.2 to 35 years (average: 9.7 years). In the present case, the patient received radiotherapy at 14 years of age. Therefore, our patient developed malignant transformation after 14 years of the possible triggering event. The different malignant morphologies reported so far include squamous cell carcinoma, odontogenic ghost cell carcinoma, low-grade myoepithelial carcinoma, ameloblastic carcinoma, and undifferentiated carcinoma. All these differential diagnoses were excluded in our case based on the morphology and immunohistochemistry findings. Although no definite diagnostic criteria for malignant craniopharyngioma have been established yet, three of the following five features have been identified in previously reported cases:
- Hypercellularity and increased nuclear–cytoplasmic ratio
- Coagulative necrosis
- Increased proliferative index or mitotic activity
- Nuclear pleomorphism and hyperchromatic nuclei
- Other features such as disruption of the basement membrane, a solid growth pattern, infiltrative growth, etc.
As the present case had a high proliferative index, an infiltrative growth pattern, disruption of the basement membrane, and hypercellularity, it was diagnosed as being malignant transformation of a craniopharyngioma. Prognosis in the case of malignant craniopharyngioma remains very poor. Although surgical resection, radiotherapy, and chemotherapy have been used in the previously reported cases, none of these have resulted in a meaningful long-term survival. Therefore, the ideal management of malignant craniopharyngiomas remains unclear.
To conclude, although malignant transformation in a craniopharyngioma is uncommon, awareness of its occurrence is important. Focal invasion, especially in an adamantinomatous craniopharyngioma, is characteristic and is not regarded as a sign of malignancy. However, dysplastic histopathological changes in a surgical specimen of craniopharyngioma, particularly in the background of previous radiotherapy, should be critically examined for signs of malignancy.
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[Figure 1], [Figure 2]